Sun J,
Zhang X,
Wang X,
Peng J,
Song G,
Di Y,
Feng F,
*,
Wang S.
*
Nanjing University and Institute of Chemistry, Chinese Academy of Sciences, Beijing,
P. R. of China
Dithiol-Activated Bioorthogonal Chemistry for Endoplasmic Reticulum-Targeted Synergistic
Chemophototherapy.
Angew. Chem. Int. Ed. 2022;
61: e202213765
DOI:
10.1002/anie.202213765
Key words
Sonogashira cross-coupling - benzothiadiazole - organic nitrite donors
Significance
Intracellular nitrite release from organic nitrite donors is an emerging approach
for inducing apoptosis via reactive nitrogen species (RNS) formation. RNS are known
to form cytotoxic peroxynitrite (OONO–) by reacting with intracellular ROS. Here, the authors present a synergistic biorthogonal
approach using 5-nitro benzothiadiazole (BTD) as the nitrite donor tethered to the
endoplasmic reticulum (ER)-targeting drug nonivamide.
Comment
This biorthogonal ‘click-to-release’ approach involves an SNAr reaction by a thiol group of the dithiol Gal-SS to release nonivamide, which causes ER stress. Another subsequent SNAr releases the nitrite through a stabilized Meisenheimer complex, which unmasks the
fluorescence of BTD. Upon irradiation, BTD sensitizes singlet oxygen to generate ROS
and synergistically causes apoptosis in liver cancer cells (HepG2).
